Bidirectional interactions between the small intestinal microbiota and bile acids in health and disease

Bile acids play an important role, on only in the digestive process where they are critical for nutrient assimilation, but they can also act as hormones that regulate host physiology as ligands for various receptors. The composition of bile acids are regulated by bacteria through enzymatic reactions such as deconjugation and dihydroxylation. Conversely, bile acids can have an impact on the composition of the gut microbiota by inhibiting growth of specific taxa. By integrating gut microbiome analyses involving shotgun metagenomic sequencing with fecal and plasma quantitative metabolomics of bile acids in both human subjects and mice, I will provide evidence that bile acids regulate the composition of the small intestinal microbiota which, in turn may have an impact on bile acid function. The inhibition of endogenouse bile acid synthesis via the activation of the farnesoid X receptor (FXR) by obetacholic acid (OCA) leads to a reversible induction of gram-positive bacteria that are found in the small intestine and are components of the diet and oral microbiota. These findings indicate that FXR activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome. Conversely, by studying the composition of the gut microbiome and bile acids in children with short bowel syndrome (SBS) we provide evidence that dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota bile salt hydrolases and glycoside hydrolases in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states such as irritable bowel syndrome.